The central objective of this program is to assess the contribution of vasoactive hormones to the pathogenesis of pulmonary vascular disease. The proposed research is a combined and coordinated attack on this problem by a group of investigators with collective skills and expertise in pulmonary medicine and in the basic sciences of biochemistry, physiology and pharmacology. The diseases or disorders to be examined are: pulmonary embolism, pulmonary edema, septic and traumatic shock, anaphylaxis, pulmonary ischemia and alveolar hypoxia. Altered metabolism and release of these vasoactive compounds will be investigated: angiotensin, bradykinin, angiotensin-converting enzyme and other peptidases, vasoactive lung peptides, vasoactive intestinal peptide, and the prostaglandins and related lipids. This list includes potent compounds that have only recently been identified and characterized, some by the applicant investigators. Additional related goals of this proposal are: evaluation of methods for the prevention, diagnosis, and management of pulmonary thromboembolism; assessment of right ventricular function in patients with pulmonary hypertension; definition of pathophysiologic responses of the pulmonary capillary bed to hypoxia and to chemical mediators, and of the effects of ischemia on pulmonary structure and ultrastructure.